Transactivator Protein (Tat)

The Transactivator protein (Tat) is a regulatory protein encoded by the human immunodeficiency virus type 1 (HIV-1). It is essential for efficient transcription of the viral genome and plays a critical role in HIV replication and pathogenesis. Tat stands for "Trans-Activator of Transcription" and consists of between 86 and 101 amino acids, depending on the viral subtype. Tat drastically enhances HIV transcription efficiency by acting as a potent transactivator by binding to an RNA stem-loop structure called the transactivation response element (TAR), located at the 5′ end of nascent HIV transcripts, which recruits cellular factors—most notably P-TEFb—which increases RNA polymerase II processivity and enables production of full-length viral RNAs. Without functional Tat protein, HIV gene expression drops dramatically due to inefficient elongation by host RNA polymerase II and viral replication becomes severely impaired.

Inhibiting Tat's interaction with TAR RNA, disrupting P-TEFb recruitment, or interfering with Tat's entry into cells.